title: Antibodies that bind complex glycosaminoglycans accumulate in the Golgi.
abstract: Light (L) chains that edit anti-DNA heavy (H) chains rescue B-cell development by suppressing DNA binding. However, exceptional editor L chains allow B cells to reach splenic compartments even though their B-cell receptors remain autoreactive. Such incompletely edited B cells express multireactive antibodies that accumulate in the Golgi and are released as insoluble, amyloid-like immune complexes. Here, we examine examples of incomplete editing from the analysis of variable to joining (VJ) gene junction of the variable (Vλx) editor L chain. When paired with the anti-DNA heavy chain, VH56R, the Vλx variants yield antibodies with differing specificities, including glycosaminoglycan reactivity. Our results implicate these specificities in the evasion of receptor editing through intracellular sequestration of IgM and the release of insoluble IgM complexes. Our findings can be extrapolated to human L chains and have implications for understanding a latent component of the Ig repertoire that could exert pathogenic and protective functions.
authors.affiliation: Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA. mradic@uthsc.edu
authors.forename: Marko
authors.initials: M
authors.lastname: Radic
authors.forename: Martin G
authors.initials: MG
authors.lastname: Weigert
authors.forename: Salar N
authors.initials: SN
authors.lastname: Khan
authors.forename: Jiong
authors.initials: J
authors.lastname: Han
authors.forename: Olga
authors.initials: O
authors.lastname: Kalinina
authors.forename: Eline T
authors.initials: ET
authors.lastname: Luning Prak
mesh_terms: D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D001483:Base Sequence; D005455:Fluorescent Antibody Technique; D006025:Glycosaminoglycans / Q000276:immunology / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D006825:Hybridomas; D007118:Immunoassay; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism*; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008163:Luminescent Measurements; D018613:Microscopy, Confocal; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D014961:X-Ray Diffraction
chemical_list: D006025:Glycosaminoglycans; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region